Topical application of the phorbol ester TPA to mouse skin causes an increase in the amount of elongation factor 2 (EF-2), a factor in eukaryotic protein synthesis, in the epidermal cytosol (2- to 3-fold) and particulate fraction (7-fold). Furthermore, as a consequence of this TPA treatment the activity of an epidermal EF-2 phosphatase is stimulated. The EF-2 phosphatase has an apparent molecular weight of around 38,000 daltons. The enzyme activity is induced as early as 45 minutes after TPA treatment and remains at the elevated level for more than 17 hours. Both of the TPA-induced effects result in an increase in unphosphorylated, i.e. active EF-2 and can be suppressed by cyclosporine A.